Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Dec 18, 2023; 13(6): 379-390
Published online Dec 18, 2023. doi: 10.5500/wjt.v13.i6.379
Pathophysiology of acute graft-versus-host disease from the perspective of hemodynamics determined by dielectric analysis
Masayuki Nagasawa
Masayuki Nagasawa, Department of Pediatrics, Musashino Red Cross Hospital, Musashino City 180-8610, Tokyo, Japan
Masayuki Nagasawa, Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Tokyo, Japan
Author contributions: Nagasawa M conceptualized and designed the study, supervised the study, drafted and revised the manuscript.
Supported by Grant-in-Aid for Scientific Research of Japan (KAKENHI), No. 2459154; and No. 15K09639.
Institutional review board statement: This study was performed in compliance with the ethical treatment policy of human and animal research participants and the Declaration of Helsinki.
Informed consent statement: Written informed consent was obtained from the guardians of each SCT patient.
Conflict-of-interest statement: All the authors have no conflicts of interest to declare.
Data sharing statement: Data available on request from the authors.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Masayuki Nagasawa, MD, PhD, Chief Physician, Department of Pediatrics, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino City 180-8610, Tokyo, Japan.
Received: September 22, 2023
Peer-review started: September 22, 2023
First decision: October 24, 2023
Revised: November 1, 2023
Accepted: December 1, 2023
Article in press: December 1, 2023
Published online: December 18, 2023

Numerous reports have demonstrated that the pathophysiology of graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT) is closely related to vascular endothelial disorders and coagulation abnormalities. We previously presented the discovery of a principle and the development of a novel instrument for measuring whole blood coagulation. This was achieved by assessing the variations in the dielectric properties of whole blood.


To investigate how GVHD affects the changes of dielectric properties of whole blood in patients with HSCT.


We examined the changes of dielectric properties of whole blood and erythrocyte proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis sequentially in patients with HSCT and compared it with clinical symptoms and inflammatory parameters of GVHD.


During severe GVHD, the dielectric relaxation strength markedly increased and expression of band3 decreased. The dielectric relaxation strength normalized with the improvement of GVHD. In vitro analysis confirmed that the increase of relaxation strength was associated with severe erythrocyte aggregates, but not with decreased expression of band3.


Severe erythrocyte aggregates observed in GVHD may cause coagulation abnormalities and circulatory failure, which, together with the irreversible erythrocyte dysfunction we recently reported, could lead to organ failure.

Keywords: Graft-versus-host disease, Dielectric relaxation, Erythrocyte, Stem cell transplantation, Coagulation

Core Tip: The pathophysiology of graft-versus-host disease (GVHD) is complex. Examination of changes in the dielectric properties of whole blood revealed that erythrocytes formed risky levels of rouleaux and aggregates in severe GVHD. In severe GVHD, oxidative stress causes degradation of erythrocyte band3 and truncation of the C-terminus of peroxiredoxin 2, resulting in decreased plasticity, increased fragility, and reduced oxygen-carrying capacity. These phenomena may underlie persistent refractory coagulopathy and circulation disorder, leading to organ damage in severe GVHD.